期刊
CANCER GENE THERAPY
卷 29, 期 6, 页码 803-813出版社
SPRINGERNATURE
DOI: 10.1038/s41417-021-00362-0
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资金
- Natural Science Foundation of Guangxi Province [2018GXNSFAA294013]
The study demonstrates that HNF4G plays a crucial role in CRC progression by promoting cell proliferation via the PI3K/AKT pathway, and miR-766-3p inhibits cell proliferation by targeting HNF4G both in vitro and in vivo. Therapies targeting the miR-766-3p/HNF4G axis may provide new treatment options for CRC.
Nuclear receptors (NRs) are a class of transcription factors that play a pivotal role in carcinogenesis, but their function in colorectal cancer (CRC) remains unclear. Here, we investigate the role NRs play in CRC pathogenesis. We found that hepatocyte nuclear factor 4 gamma (HNF4G; NR2A2), hepatocyte nuclear factor 4 alpha (HNF4A; NR2A1), and retinoid-related orphan receptor gamma (RORC; NR1F3) were significantly upregulated in CRC tissues analyzed by GEPIA bioinformatics tool. The expression of HNF4G was examined in CRC samples and cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Increased expression of HNF4G was strongly associated with high tumor-node-metastasis stage and poor prognosis. Moreover, overexpression of HNF4G significantly promoted the proliferation of CRC cells in vitro. Next, we found that HNF4G promoted CRC proliferation via the PI3K/AKT pathway through targeting of GNG12 and PTK2. In addition, HNF4G was verified as a direct target of microRNA-766-3p (miR-766-3p). miR-766-3p inhibited the proliferation of CRC cells by targeting HNF4G in vitro and in vivo. Collectively, our study indicates that miR-766-3p reduces the proliferation of CRC cells by targeting HNF4G expression and thus inhibits the PI3K/AKT pathway. Therefore, development of therapies which target the miR-766-3p/HNF4G axis may aid in the treatment of CRC.
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